Activation of T cells is a complex process involving cell membrane, cytoplasmic and nuclear events. These events enable T cells to proliferate and exert their immunoregulatory function. The purpose of these studies is to define the effects of biologic agents used for the therapy of immune mediated renal diseases (glucocorticoids, cyclosporine A), as well as those produced at the site of inflammation (prostaglandin E2, transforming growth factor-beta), on molecular events associated with T cell activation. T cell activation through its antigen specific receptor results in increased intracellular calcium and activation of protein kinase C (PKC). Increased intracellular calcium, in turn, activates calmodulin (CaM) dependent kinases, such as CaM kinase II and phosphatases, such as calcineurin. Glucocorticoids downregulate the activity of CaM kinase II, but not PKC, during T cell activation by upregulating protein phosphatases 1 and/or 2A, but not 2B. Both cyclic AMP elevating agents and glucocorticoids inhibit calcineurin-dependent pathways for T cell activation (calcineurin being a calcium/calmodulin-dependent 2B phosphatase).